Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy

Abstract

Autoimmunity to antigens of the central nervous system is usually considered detrimental. T cells specific to a central nervous system self antigen, such as myelin basic protein, can indeed induce experimental autoimmune encephalomyelitis, but such T cells may nevertheless appear in the blood of healthy individuals. We show here that autoimmune T cells specific to myelin basic protein can protect injured central nervous system neurons from secondary degeneration. After a partial crush injury of the optic nerve, rats injected with activated anti-myelin basic protein T cells retained approximately 300% more retinal ganglion cells with functionally intact axons than did rats injected with activated T cells specific for other antigens. Electrophysiological analysis confirmed this finding and suggested that the neuroprotection could result from a transient reduction in energy requirements owing to a transient reduction in nerve activity. These findings indicate that T-cell autoimmunity in the central nervous system, under certain circumstances, can exert a beneficial effect by protecting injured neurons from the spread of damage.

CNS‐infiltrating CD4+ T lymphocytes contribute to murine spinal nerve transection‐induced neuropathic pain

“…Differential expression in cytokine/chemokine receptor and/or adhesion molecules on infiltrating CD4 + T lymphocytes determines their ability to migrate into the CNS and their specific interactions with CNS-resident cells [23,24]. Increased lumbar spinal cord IP-10 expression post L5Tx (unpublished data) would suggest a Th1 phenotype of the observed CNS-infiltrating CD4 + T lymphocytes, which is supported by the fact that adoptive transfer of Th1 cells produced hypersensitivity in nude rats following CCI [8].…”

T cell independent mechanism for copolymer‐1‐induced neuroprotection

“…Although the earlier studies showed that autoimmune T cells could protect injured neurons from ongoing degeneration, this beneficial effect was counterbalanced by their propensity for inducing destructive autoimmunity [45]. To overcome this deleterious effect, T cells that cross-react weakly with autoantigens without Several studies have demonstrated a significant effect of Cop-1 on the innate cells of the immune system, such as macrophages, DC, and monocytes [53][54][55][56].…”

Inflammation and spinal cord injury: Infiltrating leukocytes as determinants of injury and repair processes

“…Therefore, boosting the immune responses to CNS injury under certain conditions may be more beneficial than harmful to functional regeneration (58) . Implantation of activated macrophages (86) or T-lymphocyte mediated immune activity, achieved by either adoptive transfer or active immunization (87)(88)(89)(90) , enhances recovery from spinal cord injury by conferring neuroprotection or regeneration. Although the concept of neuroprotective autoimmunity is intriguing, there is no definitive mechanism that explains its efficacy.…”